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Smoking in Cancer Care (PDQ®)

Health Professional Version
Last Modified: 06/20/2014

Poorer Treatment Response in Cancer Patients

Evidence exists for substantial medical advantage to an individual quitting smoking once cancer is diagnosed. There is substantial evidence that continued smoking may reduce the effectiveness of treatment and increase the likelihood of a second cancer. (Refer to the Smoking as a Risk Factor for Second Malignancy section of this summary for more information.) Continued smoking may also worsen side effects of treatment,[1] although the direct evidence for this is surprisingly limited because few studies have evaluated this issue.

If one extrapolates from the extensive evidence of the effects of smoking on cardiovascular disease, pulmonary functioning, immunosuppression, and wound healing due to vasoconstriction and the fairly rapid reduction of some effects after smoking cessation,[2,3] these results might also apply to cancer patients, particularly if surgical management or lung functioning is involved. For example, one study outlined a model of cardiopulmonary toxicities in response to various antineoplastic therapies that may be potentiated by tobacco use. More specifically, smokers treated with bleomycin or carmustine showed higher levels of pulmonary fibrosis and restrictive lung disease, and the anthracyclines led to higher risk of cardiomyopathy in smokers.[4]

In a study of patients with advanced head and neck cancer who underwent radiation therapy,[5] patients who continued to smoke during radiation therapy suffered mucositis for a longer time (23.4 weeks) than did patients who quit at the time of radiation therapy and remained abstinent (13.6 weeks) or patients who remained abstinent for at least a month after treatment (18.3 weeks). Extended mucositis may be associated with permanent alteration in appearance. Studies show that perioperative and long-term complications are considerably higher in patients with head and neck cancer who continue to smoke.[6] In one study, patients receiving induction chemotherapy for acute myeloid leukemia who continued to smoke were more likely to experience severe pulmonary infection (26% vs. 18%), although overall survival rates did not differ in adults older than 60 years.[7] After radiation therapy for laryngeal carcinoma, patients who continue to smoke may be less likely to regain satisfactory voice quality.[8]

Another area of reasonable concern for patients who continue to smoke is the rate of general complications after any type of surgery. It is documented that wound healing postsurgery is slowed in smokers because both nicotine and carbon monoxide cause vasoconstriction, inhibition of epithelization, and creation of cellular hypoxia.[9,10] In one study of predictors of complications after resection in lung cancer patients, a history of smoking doubled the likelihood of complications, but smoking at the time of admission for surgery did not.[11] However, no detailed information on the time since smoking had ceased was provided.

One study found decreased response rates and survival rates in patients with head and neck cancer who continued to smoke during treatment. Patients who continued to smoke had a significantly lower rate of complete response to radiation therapy (45% vs. 74%) and 2-year survival (39% vs. 66%). Recent quitters were more similar to long-term quitters than to continued smokers in survival likelihood at 18 months.[12]

Another study also showed an effect of continued smoking on survival rates in patients with head and neck cancer.[13] Those who stopped smoking doubled their chance of survival, irrespective of extent of disease at diagnosis; after 2 years, survival of quitters approached that of nonsmokers. Relative risk of recurrence in quitters was about double that of nonsmokers; in those who continued to smoke after diagnosis, relative risk of recurrence quadrupled, regardless of the amount they smoked. One study failed to find significant differences in prognosis in resected stage I non-small cell lung cancer patients on the basis of smoking status; the recurrence and death rates in both former and current smokers did not differ but were double to triple the rates in newer smokers.[14] These differences failed, however, to reach statistical significance because of the small number of newer smokers; in addition, the lack of differences between former versus current smokers was hard to interpret because no definitions were provided.

In another study, a consistent trend was found in patients with small cell cancer: continued smokers had the poorest survival, followed by patients who quit at diagnosis, then by patients who had quit on average 2.5 years before diagnosis.[15] Although survival curves of recent ex-smokers did not differ statistically from continued smokers, perhaps because of small numbers, no continued smokers (n = 57) survived past 131 weeks, whereas six of those who quit at diagnosis (n = 35) were in complete remission at 1 and 2 years.

The relationships between smoking, disease recurrence, and mortality rates for prostate cancer have been examined. Studies have found an association between continued smoking and earlier recurrence [16,17] and increased mortality.[18] In a study of 1,416 men who underwent radical prostatectomy, recurrence occurred after a mean of 7.3 years in 34.3% of current smokers, 14.8% of former smokers, and 12.1% of those who had never smoked.[17] Another study found higher 5-year mortality rates in patients with stage D2 disease (88% vs. 63%) and non–stage A disease (39% vs. 17%).[16] In a prospective observational study of 5,366 men, prostate cancer–specific death rates were 15.3 per 1,000 person-years for current smokers versus 9.6 per 1,000 person-years for those who had never smoked. Prostate cancer patients who quit smoking for 10 years or longer had mortality rates similar to those of nonsmokers.[18]

References
  1. Des Rochers C, Dische S, Saunders MI: The problem of cigarette smoking in radiotherapy for cancer in the head and neck. Clin Oncol (R Coll Radiol) 4 (4): 214-6, 1992.  [PUBMED Abstract]

  2. U.S. Department of Health and Human Services: The Health Benefits of Smoking Cessation. A Report of the Surgeon General. Rockville, Md: 1990. DHHS Publ No. (CDC) 90-8416. 

  3. U.S. Department of Health and Human Services: A Report of the Surgeon General: How Tobacco Smoke Causes Disease: What It Means to You. Atlanta, Ga: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010. Also available online. Last accessed June 12, 2014. 

  4. Tyc VL, Hudson MM, Hinds P, et al.: Tobacco use among pediatric cancer patients: recommendations for developing clinical smoking interventions. J Clin Oncol 15 (6): 2194-204, 1997.  [PUBMED Abstract]

  5. Rugg T, Saunders MI, Dische S: Smoking and mucosal reactions to radiotherapy. Br J Radiol 63 (751): 554-6, 1990.  [PUBMED Abstract]

  6. Wein RO: Preoperative smoking cessation: impact on perioperative and long-term complications. Arch Otolaryngol Head Neck Surg 135 (6): 597-601, 2009.  [PUBMED Abstract]

  7. Chelghoum Y, Danaïla C, Belhabri A, et al.: Influence of cigarette smoking on the presentation and course of acute myeloid leukemia. Ann Oncol 13 (10): 1621-7, 2002.  [PUBMED Abstract]

  8. Karim AB, Snow GB, Siek HT, et al.: The quality of voice in patients irradiated for laryngeal carcinoma. Cancer 51 (1): 47-9, 1983.  [PUBMED Abstract]

  9. Gritz ER, Kristeller J, Burns DM: Treating nicotine addiction in high-risk groups and patients with medical co-morbidity. In: Orleans CT, Slade J, eds.: Nicotine Addiction: Principles and Management. New York, NY: Oxford University Press, 1993, pp 279-309. 

  10. U.S. Department of Health and Human Services: The Health Consequences of Smoking: Cardiovascular Disease. A Report of the Surgeon General. Rockville, Md.: DHHS Publication No. (PHS) 84-50204, 1983. 

  11. Kearney DJ, Lee TH, Reilly JJ, et al.: Assessment of operative risk in patients undergoing lung resection. Importance of predicted pulmonary function. Chest 105 (3): 753-9, 1994.  [PUBMED Abstract]

  12. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993.  [PUBMED Abstract]

  13. Stevens MH, Gardner JW, Parkin JL, et al.: Head and neck cancer survival and life-style change. Arch Otolaryngol 109 (11): 746-9, 1983.  [PUBMED Abstract]

  14. Gail MH, Eagan RT, Feld R, et al.: Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group. Cancer 54 (9): 1802-13, 1984.  [PUBMED Abstract]

  15. Johnston-Early A, Cohen MH, Minna JD, et al.: Smoking abstinence and small cell lung cancer survival. An association. JAMA 244 (19): 2175-9, 1980.  [PUBMED Abstract]

  16. Daniell HW: A worse prognosis for smokers with prostate cancer. J Urol 154 (1): 153-7, 1995.  [PUBMED Abstract]

  17. Joshu CE, Mondul AM, Meinhold CL, et al.: Cigarette smoking and prostate cancer recurrence after prostatectomy. J Natl Cancer Inst 103 (10): 835-8, 2011.  [PUBMED Abstract]

  18. Kenfield SA, Stampfer MJ, Chan JM, et al.: Smoking and prostate cancer survival and recurrence. JAMA 305 (24): 2548-55, 2011.  [PUBMED Abstract]